SAN FRANCISCO, May 19, 1996 — A year following a family reunion that initiated an intensive study to identify the gene for hereditary pancreatitis, researchers from the University of Pittsburgh Medical Center (UPMC) say they have narrowed their search to a small area on one chromosome. The finding was made possible in large part due to the assistance of an extended family affected by this incurable disease for generations. Results from the Midwest Multi-Center Pancreatic Study Group, which also includes the University of Kentucky at Lexington and the University of Cincinnati, will be presented during Digestive Disease Week (DDW), a series of scientific meetings May 19-22 being attended by 10,000specialists in gastrointestinal diseases.
The researchers, led by the UPMC's David Whitcomb, M.D., Ph.D., and Garth Ehrlich, Ph.D., also plan to reveal the results to their collaborators -- a family of more than 100 living relatives located primarily in eastern Kentucky and western Virginia -- at a picnic planned for Memorial Day. Thirty-six of the 103 relatives in the study have the painful disorder, more than half since before the age of five.
Genetic study of this family, which had been initiated by a University of Indiana physician more than 25 years ago, has been practical only in the last two to three years due to an emerging technology called microsatellite-based familial genetic linkage analysis. The technology permits tiny markers along strands of DNA to be amplified. By pinpointing identical markers and their location on a specific chromosome, researchers follow the inheritance of certain diseases.
At DDW, Dr. Whitcomb will report the gene for hereditary pancreatitis lies somewhere on chromosome 7q35, a location not before hypothesized by researchers in the field. Details of the study are to be published in the June issue of the medical journal Gastroenterology.
"This represents a major advancement. We are very close to understanding the genetic basis for this disorder, which we hope will enable us to develop strategies to prevent or control hereditary pancreatitis in families that are affected, vastly improving their quality of life," says Dr. Whitcomb, who is an assistant professor of medicine in the division of gastroenterology and hepatology at the UPMC.
"Although the gene has not yet been identified, using the genetic markers we've located that map near the gene, we can tell with 95 percent accuracy if a person has inherited the high risk gene. Implications for this family and others are great," adds Dr. Whitcomb.
"Inheritance of hereditary pancreatitis appears to be very complex. Further study may take months or years to identify the gene, depending on whether the gene has or has not been previously identified in another guise," says Dr. Ehrlich, associate professor of pathology and otolaryngology at the UPMC and co-investigator of the project.
Information obtained through interviews, questionnaires, and blood samples, which were collected with the assistance of a family member who is a nurse, is helping researchers to piece together the genetic puzzle. Family bibles and other family records have enabled the team to construct a family tree of 500 relatives spanning eight generations.
"This family has been incredibly helpful. It became very apparent at our first picnic a year ago that these people wanted answers," says Dr. Whitcomb.
Hereditary pancreatitis occurs in pockets throughout the world. Hence, in some areas, like the location of the study family, it is quite common, whereas in other geographic regions it is very rare.
The disease typically begins between the ages of five and 10 with an acute attack of abdominal pain. The pancreas becomes inflamed as the digestive enzymes intended for the intestine leak out of the cells that produce them and the pancreas begins digesting itself. After repeated attacks and scarring of the organ, a chronic condition develops that is characterized by constant pain, nausea and vomiting, as well as by weight loss due to malabsorption of food. It often leads to severe complications, including diabetes and pancreatic cancer, which occurs at a rate of more than 50 times higher than in the general population. There is no treatment for hereditary pancreatitis.
According to other findings to be presented at DDW by Dr. Whitcomb, 84 percent of the affected family members reported having had more than 11 acute attacks, lasting more than five days in more than half of them and requiring hospitalization in two thirds. Thirty percent have developed diabetes and 33 percent have had surgery to remove their gallbladders because of gallstones.
To further explore this finding, ultrasound studies using a portable device will be offered to family members at this year's Memorial Day picnic. The picnic is expected to attract additional family members living in other states, who, like their relatives, were notified through a newsletter published by the researchers on a regular basis for the family. At the picnic, Dr. Whitcomb and Lawrence Gates, M.D., of the University of Kentucky, will present what has been learned thus far with special emphasis on their findings' implications to individual family members. Drs. Gates and Whitcomb will be joined by others on the research team, including Dr. Ehrlich from the UPMC and Charles Ulrich, M.D., and Stephen Martin, M.D., both from the University of Cincinnati.